Department of Microbiology and Immunology, Hollings Cancer Center, Medical University of South Carolina, Charleston, SC, 29425, USA.
Children's Hospital Boston, Harvard Medical School, Boston, MA, 02115, USA.
J Hematol Oncol. 2018 Feb 20;11(1):24. doi: 10.1186/s13045-018-0570-z.
GARP (glycoprotein-A repetitions predominant) is a type I transmembrane cell surface docking receptor for latent transforming growth factor-β (TGF-β) that is abundantly expressed on regulatory T lymphocytes and platelets. GARP regulates the availability of membrane-bound latent TGF-β and modulates its activation. For this reason, GARP expression on immune and non-immune cells is involved in maintaining peripheral tolerance. It plays an important role in preventing inflammatory diseases such as allergy and graft versus host disease (GvHD). GARP is also frequently hijacked by cancer cells to promote oncogenesis. This review summarizes the most important features of GARP biology described to date including gene regulation, protein expression and mechanism in activating latent TGF-β, and the function of GARP in regulatory T cell biology and peripheral tolerance, as well as GARP's increasingly recognized roles in platelet-mediated cancer immune evasion. The promise for GARP-targeted strategy as a novel immunotherapy of cancer is also highlighted.
GARP（糖蛋白-A 重复为主）是一种 I 型跨膜细胞表面衔接受体，可与潜伏转化生长因子-β（TGF-β）结合，在调节性 T 淋巴细胞和血小板中大量表达。GARP 调节细胞膜结合的潜伏 TGF-β的可用性，并调节其激活。由于这个原因，免疫和非免疫细胞上的 GARP 表达参与维持外周耐受。它在预防过敏和移植物抗宿主病（GvHD）等炎症性疾病方面发挥着重要作用。GARP 还经常被癌细胞劫持，以促进肿瘤发生。本综述总结了迄今为止描述的 GARP 生物学的最重要特征，包括基因调控、蛋白表达和激活潜伏 TGF-β的机制，以及 GARP 在调节性 T 细胞生物学和外周耐受中的功能，以及 GARP 在血小板介导的癌症免疫逃逸中日益被认可的作用。还强调了 GARP 靶向策略作为癌症新免疫疗法的前景。
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